Recombinant human bone morphogenetic protein-2 (rhBMP-2) is being evaluated as a bone growth inducer for dental and orthopedic indications. Dose responses have been equivocal in the delivery systems investigated and bone marrow cultures produced more robust osteoblastic characteristics from sustained application of rhBMP-2 than from short term exposure. The research proposed attempts to answer the fundamental question of whether a sustained released of rhBMP-2 within a defect site, grows bone better than immediate release. Rabbit calvarial defects will be the animal model for bone growth and rat calvarial defects will be the in vivo release model. Delivery systems will be produced from porous poly(lactide-co glycolide) (PLGA) microspheres to which rhBMP-2 has been incorporated by absorption and lyophilization implantable matrices are produced by suspending protein-loaded particles in 2% carboxymethyl cellulose (CMC), lyophilizing, and cutting the dried material to size. RhBMP-2 release profiles will be controlled by selection of PLGA and process parameters to obtain porous particles of similar size and morphology. RhBMP-2 binding and release will be performed to select two polymer-types, one capable of sustained release and another capable of immediate release, for production and implantable matrices. In the first animal experiment, immediate or sustained release matrices will be implanted into 7.9 mm circular defects in rabbit calvaria. Bone, scored by inflammation, new bone amount, new bone type, fibroblast levels, fibrosis, fat, defect edge, and vascularity will be evaluated six weeks post implantation. In the second animal experiment, matrices containing radiolabeled rhBMP-2 will be implanted in rat calvaria and removed at set times for analysis. The hypothesis tested will be: 1) Porous particles of various PLGA types can be prepared with similar morphology. 2) The desired release profile can be obtained from one thing or a blend of the PLGA microspheres. 3) In a rabbit calvarial defect, more new bone will result from delivering a dose of rhBMP-2, continuously, over a four to six week period, than from delivery of the same dose in three to five days. 4) In vivo release of rhBMP-2 determined in rats will correlate to in vitro release. Knowledge of how tissue repair, vascularization and nerve growth. Additionally, this work will provide further insight into the delivery of proteins in a sustained, controlled manner.